This research is designed to investigate the role played by drug receptor sites in regulating the proliferation and differntiation of the hemopoietic stem cell. The study seeks to uncover receptor sites that switch DNA synthesis on or off in hemopoietic cells. Any rrle played by drug receptors in the leukemogenic process (whether during the spontaneous development of leukemia or in leukemias artificially induced by chemicals or by viruses), in adverse effects on bone marrow of clinically useful drugs, and in immune reactions specifically, the graft versus host reaction, will be studied. The phosphodiesterase enzymes vary in their sensitivity to a particular inhibitor. By investigating a variety of agents that inhibit phosphodiesterases an attempt will be made to manipulate the cell cycle in tissues such as bone marrow. Such manipulation of the cell cycle may be a means of altering th sensitivity of tissues to cycle-dependent anticancer agents or cycle-dependent drugs used in immunosuppressive treatment. Hence, attempts will be made to promote a more selective action of cytotoxic drugs on specific tissues. It is not known whethr drug receptors play a direct role in the antiproliferative action of cytotoxi agents. Studies will be designed to determine whether previous blocking of receptor sites (without alteration of the cell cycle state) would modify the cell-killing action of such compounds. The hemopoietic stem cell of bone marrow is still to be identified. The triggering of bone marrow stem cells into DNA synthesis by low concentrations of isoproterenol and acetylcholine suggest that drug molecules may concentrate in cells responding to these agents. Using the autoradiographic technique, efforts will be made to see whether such concentration of mollcules takes place. Such a study may serve to better recognise the hemopoietic stem cell.